1. Field of the Invention
The present invention relates generally to the fields of analytical sensing, imaging, and monitoring. More specifically, the present invention relates to a method and system utilizing time-resolved optoacoustic technique to monitor in real time tissue optical properties, which in turn depend on glucose concentration in blood.
2. Description of the Related Art
There is a continued significant effort by many companies and scientific groups to quantify blood glucose concentration with noninvasive and minimally invasive procedures. A number of patents have been issued to protect various noninvasive technologies for glucose monitoring. Noninvasive procedures employ various optical approaches.
In previously disclosed approaches, glucose was detected directly as a chromophore (absorbing molecule), Raman scattering molecule, dichroic (polarization rotating) molecule or fluorescent complex with a strongly fluorescent dye and an osmolyte that changes tissue scattering. All these approaches utilize measurement of signal amplitude in response to tissue irradiation with light. The main weakness of all these pure optical approaches is low signal to noise ratio and/or low specificity to glucose. Low signal to noise ratio results from the fact that glucose is present in tissues in millimolar concentration, while other interfering molecules are present in greater concentrations. Low specificity results from the fact that optical properties of glucose overlap with optical properties of interfering molecules. All previously disclosed methods have one additional inherent limitation associated with incapability to measure changes in optical properties along the photon path inside the tissue. Only signals integrated over the entire optical path in tissue can be determined by standard optical. methods. Time resolved, phase-resolved and interferometric optical methods possess limitations that are not currently resolved.
MacKenzie et al. (WO 98/38904), Rozensweig et al. (U.S. Pat. No. 5,657,754), and Chou (U.S. Pat. No. 5,941,821) disclosed the use of photoacoustic and thermoacoustic spectroscopy for glucose monitoring. These photoacoustic techniques utilize high sensitivity of acoustic detection. However, these technologies determine the concentration of glucose from an acoustic signal amplitude. The method of photoacoustic spectroscopy does not measure neither tissue scattering, nor profiles of optically induced acoustic waves in tissues irradiated under conditions of stress confinement in the tissue volume of interest. The detection of profiles of optically induced acoustic waves instead of detection of either optical amplitude or acoustic amplitude makes a significant difference in the signal-to-noise ratio.
An important ability of glucose to decrease tissue scattering based on its properties as osmolyte was first described by Gratton et al. (U.S. Pat. No. 5,492,118). However, this prior art disclosed pure optical less precise means to measure tissue scattering. These means do not utilize measurement of profiles of spatial distribution of tissue scattering replicated in profiles of acoustic waves, and therefore, can not yield sufficiently sensitive and reliable method to measure glucose concentration in tissues.
The prior art is deficient in the lack of effective means of noninvasive monitoring of glucose concentration in real time. The present invention fulfills this long-standing need and desire in the art.
The present invention is directed to a method and system of real-time optoacoustic monitoring of tissue optical scattering for the purpose of providing quantitative information about glucose concentration in blood.
In one embodiment of the present invention, there is provided a method of noninvasive monitoring of glucose concentration in real time using laser optoacoustic imaging, comprising the steps of irradiating a tissue of interest with at least one short optical pulse to create a distribution of absorbed optical energy in the tissue; generating optothermally-induced pressure profile under conditions of temporal pressure confinement in the irradiated tissue; detecting the pressure profile with at least one acoustic transducer, wherein the acoustic transducer is a wide-band transducer capable of detecting the entire range of ultrasonic frequencies contained in the pressure profile; recording the ultrasound signal magnitude along the pressure profile by an electronic system; analyzing the spectrum of ultrasonic frequencies of the pressure profile, wherein a change in the ultrasonic frequency indicates a change in tissue scattering coefficient, which in turn is proportional to a change in glucose concentration in the tissue, which further correlates with a change of glucose concentration in blood.
The method disclosed herein can be utilized in systems measuring tissue optical properties in vivo and, in principle, can be applied for detection of other tissue analytes influencing tissue optical properties. In another embodiment of the present invention, there is provided a system for monitoring glucose concentration noninvasively in real time, comprising a pulsed optical source to produce a pressure profile confined in a volume of tissue of interest; a light delivery system for delivery of radiation to the tissue; at least one acoustic transducer to detect the pressure profile in the tissue, wherein the acoustic transducer is capable of detecting the entire range of ultrasonic frequencies contained in the pressure profile; an electronic system for recording and processing of the detected pressure profile; and a computer with software analysis of the detected pressure profile and calculation the glucose concentration.
Other and further aspects, features, and advantages of the present invention will be apparent from the following description of the presently preferred embodiments of the invention given for the purpose of disclosure.